Isoamylamine → 3-[3,5-Bis(trifluoromethyl)phenylamino]-2-cyano-3-(3-methylbutylamino)-2-propenenitrile

HRID 618786Notes

Reaction equation

HRID 618786 reaction equation
[C:1](#[N:5])[CH2:2][C:3]#[N:4].[F:6][C:7]([F:22])([F:21])[C:8]1[CH:9]=[C:10]([N:18]=[C:19]=S)[CH:11]=[C:12]([C:14]([F:17])([F:16])[F:15])[CH:13]=1.[CH3:23][CH:24]([CH3:28])[CH2:25][CH2:26][NH2:27].S([O-])([O-])(=O)=O.[Mg+2]>C(Cl)Cl.[Hg]=O.C(N(CC)CC)C>[F:6][C:7]([F:22])([F:21])[C:8]1[CH:9]=[C:10]([NH:18][C:19]([NH:27][CH2:26][CH2:25][CH:24]([CH3:28])[CH3:23])=[C:2]([C:1]#[N:5])[C:3]#[N:4])[CH:11]=[C:12]([C:14]([F:17])([F:16])[F:15])[CH:13]=1

Participants

8

Reactant 4

HCID 7894IsoamylamineHCID 8010MalononitrileHCID 24083Sulfuric acid magnesium salt (1:1)HCID 27333953,5-Bis(trifluoromethyl)phenyl isothiocyanate

Product 1

HCID 218484673-[3,5-Bis(trifluoromethyl)phenylamino]-2-cyano-3-(3-methylbutylamino)-2-propenenitrileYield 63%

Reagents, catalysts & solvents 3

HCID 30856Mercuric oxideCatalystHCID 6344DichloromethaneSolvent2×HCID 8471TriethylamineSolvent

Procedure

To a solution of malononitrile (0.33 g, 5.00 mmol) in DCM at 0° C. first 3,5-bis(trifluoromethyl)phenylisothiocyanate (1.41 g, 5.20 mmol) and then triethylamine (1.0 mL) were added. The mixture was stirred at room temperature for 1 h 45 min and then DCM (5 mL), 3-methylbutylamine (1.0 mL, 8.60 mmol), magnesium sulfate (0.57 g) and mercury(II) oxide (2.54 g, 11.7 mmol) were added. The resulting mixture was stirred at room temperature for 17 h, whereby it turned black. This mixture was then filtrated (Celite), diluted with DCM (60 mL), washed with an ice-cold mixture of water (100 mL) and conc. HCl (2.0 mL), with brine (3×50 mL), dried (magnesium sulfate) and concentrated. The residue was purified by column chromatography (50 g silica gel, heptane/ethyl acetate gradient), to yield 1.22 g (63%) of the title compound as a foam. This foam could be crystallized from toluene/heptane, yielding 1.08 g of almost colourless crystals, mp. 158-159° C. 1H NMR (300 MHz, DMSO-d6): δ=0.87 (d, J=7 Hz, 6H), 1.45 (q, J=7 Hz, 2H), 1.60 (nonett, J=7 Hz, 1H), 3.31 (m, 2H), 7.72 (s, 2H), 7.78 (s, 1H), 8.22 (s, br, 1H), 9.79 (s, 1H); 13C NMR (75 MHz, DMSO-d6): δ=22.04, 24.99, 36.85, 37.14, 59.66, 116.52, 117.52, 121.21, 123.02 (q, J=275 Hz), 131.02 (q, J=33 Hz), 141,35, 161.27. Anal. Calcd. for C17H16F6N4 (390.33): C, 52.31; H, 4.13; N, 14.35. Found: C, 52.80; H, 4.29; N, 13.83.

Workup

  1. stirringThe resulting mixture was stirred at room temperature for 17 h
  2. filtrationThis mixture was then filtrated (Celite)
  3. additiondiluted with DCM (60 mL)
  4. washwashed with an ice-cold mixture of water (100 mL) and conc. HCl (2.0 mL), with brine (3×50 mL)
  5. dry with materialdried (magnesium sulfate)
  6. concentrationconcentrated
  7. customThe residue was purified by column chromatography (50 g silica gel, heptane/ethyl acetate gradient)

Sources & evidence

ORD record
ord-d74985fabfea42108f01739a465a3be8
Source dataset
uspto-grants-1999_09
Patent number
US05955548

Reaction notes

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